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Combining atomic-level Molecular Dynamics with coarse-grained Monte-Carlo dynamics

Combining atomic-level Molecular Dynamics with coarse-grained Monte-Carlo dynamics Andrzej Koliński Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw http://www.biocomp.chem.uw.edu.pl. Bioinformatics 2013 / BIT13, 26-29 June 2013, Toruń, Poland.

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Combining atomic-level Molecular Dynamics with coarse-grained Monte-Carlo dynamics

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  1. Combining atomic-level Molecular Dynamics with coarse-grained Monte-Carlo dynamics Andrzej Koliński Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw http://www.biocomp.chem.uw.edu.pl Bioinformatics 2013 / BIT13, 26-29 June 2013, Toruń, Poland

  2. All-atom MD with explicit water • Atomic-Level Characterization of the Structural Dynamics of Proteins,Science, 2010 • How Fast-Folding Proteins Fold,Science, 2011 1 milisecondsimulations ANTON - David E. Shaw group

  3. Simulations of near-native dynamics seem to be essentially force-field independent. Different all-atom force-fields (explicit water) are: - able to fold a protein into its native tertiary structure - inconsistent in the description of a folding pathway M. Rueda, C. Ferrer-Costa, T. Meyer, A. Perez, J. Camps, A. Hospital, J. L. Gelpi, M. Orozco, A consensus view of protein dynamicsProc. Natl. Acad. Sci. U.S.A. 104:796−801, 2007

  4. Coarse-grained models

  5. Coarse-grained models of moderate resolution (~102 faster than all-atom MD) Lattice Kolinski et al. Continuous Baker et al. Liwo et al.

  6. CABS model Force field Short range conformational propensities Context-dependent pairwise interactions of side groups A model of main chain hydrogen bonds Interaction parameters are modulated by the predicted secondary structure and account for complex multibody interactions andthe averaged effect of solvent Sampling – Monte Carlo dynamics A. Kolinski,Protein modeling and structure prediction with a reduced representation Acta Biochimica Polonica 51:349-371,2004

  7. Reconstruction &optimization procedure protein backbone reconstruction side chain reconstruction all-atom minimization step

  8. Protein dynamics All-atom MD(A – Amber, C – Charmm, G – Gromos and O – OPLS/AA force-fields) is consistent with CABS stochastic dynamics (after a proper renormalizations) at short time-scales (10 ns) M. Jamroz, M. Orozco, A. Kolinski, S. Kmiecik, A Consistent View of Protein Fluctuations from All-atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-based Force-field, J. Chem. Theory Comput. 9:19–125, 2013 J. Wabik, S. Kmiecik, D. Gront, M. Kouza, A. Kolinski, Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics, International Journal of Molecular Sciences 14:9893-9905, 2013.

  9. CABS models reconstructed all-atom models (AMBER) Kmiecik, D. Gront, M. Kouza, A. Kolinski, From Coarse-Grained to Atomic-Level Characterizationof Protein Dynamics: Transition State for the Folding of B Domain of ProteinA, J. Phys. Chem. B 116:7026-7032, 2012

  10. Dynamics: CABS and all-atoms MD

  11. Example of residue fluctuation profiles

  12. Benchmarks summary

  13. http://biocomp.chem.uw.edu.pl/CABSflex

  14. CABS-flex PDB: 1BSN, F1-ATPase subunit, 138 AA

  15. CABS-flex PDB: 1BSN, F1-ATPase subunit, 138 AA

  16. CABS-flex PDB: 1BHE, polygalacturonase, 376 AA

  17. CABS-fold: server for protein structure prediction http://biocomp.chem.uw.edu.pl/CABSfold

  18. CABS in structure prediction M. Blaszczyk, M. Jamroz, S. Kmiecik, A. Kolinski, CABS-fold: server for the novo and consensus-based prediction of protein structure,Nucleic Acids Research, 2013

  19. Structure prediction (de-novo) The predicted models (colored in rainbow) are superimposed on native structures (colored in magenta) Modelingaccuracy could be highly improved when combined with compartive modeling. A. Kolinski, J. M. Bujnicki, Generalized protein structure prediction based on combination of fold-recognition with de novo folding and evaluation of models, Proteins 61(S7):84-90, 2005

  20. Structureprediction (homologymodeling) CASP9 examples 9th Community Wide Experiment on theCritical Assessment of Techniques for Protein Structure Prediction

  21. CABS – docking and interactionsSimulations of induced folding (binding) of intrisingly disordered protein pKIG with KIX domain

  22. CABS – docking and interactionsSimulations of induced folding (binding) of intrisingly disordered protein pKIG with KIX domain

  23. Summary: • CABS could be easily combined with all-atomMolecular Dynamics and usedin studies of protein dynamics, interactions and structure prediction • LTB servers based on CABS tools: • URL: http://biocomp.chem.uw.edu.pl/CABSfold • URL: http://biocomp.chem.uw.edu.pl/CABSflex • M. Jamroz, A. Kolinski & S. Kmiecik, CABS-flex: server for fast simulation of protein structure fluctuations,Nucleic Acids Research, 1-5, 2013 • M. Blaszczyk, M. Jamroz, S. Kmiecik, A. Kolinski, CABS-fold: server • for the novo and consensus-based prediction of protein structure,Nucleic Acids Research 1-6, 2013

  24. Thank you! Co-authors: Drs. Sebastian Kmiecik, Michał Jamróz, Dominik Gront, Maciej Błaszczyk, Mateusz Kurciński, Jacek Wabik and others ….

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